The long-term objective of this study will be to elucidate the role of cyclophilin (CyP), a specific cytosolic binding protein for cyclosporin A (CsA), and a putative natural ligand in regulation of the immune system and to extend these findings to the treatment of T cell and other neoplasms. Specific aims include: (1) isolation of the natural ligand for CyP as well as CyP-binding proteins from neoplastic or otherwise activated cells; (2) further characterization of the structure of major and minor isoforms of CyP in neoplastic tissues and normal organs that are targets of toxicity with an analysis of factors mediating their possible interconversion; (3) implementation of a clinical protocol to study the therapeutic efficacy of CsA in the treatment of selected T-cell leukemias and lymphomas and determination of whether the growth characteristics of CsA-sensitive cells from these patients are mediated by CyP or its natural ligand. The postulated natural ligand will be prepared by CyP affigel matrix chromatography and other techniques from cell extracts, supernatants and sera. Lysine-C digests of CyP will be used to determine the degree of homology between normal and neoplastic cells with respect to major and minor CyP species. Measurements of the interconversion of isoforms of CyP will employ several biological systems capable of triggering the cellular activation and analysis of the species by gel isoelectrofocusing and radioautography. The large number of patients currently seen at the Yale mycosis fungoides clinic as well as those with childhood acute lymphocytic leukemia treated by the Pediatric Service provide ample clinical material for the therapeutic trial as well as studies of surface markers, histology and cytogenetics. Analysis of CyP content, physical properties and cellular localization of CyP will be performed by LH-20 assay, agarose electrophoresis, and "Western" blot assay utilizing monoclonal or polyclonal antisera to CyP.